title: Circulating collagen metabolites, myocardial fibrosis and heart failure in aortic valve stenosis.
abstract: OBJECTIVE
  Myocardial fibrosis predisposes to heart failure in aortic valve stenosis. The study aim was to determine the value of: (i) circulating collagen metabolites as biomarkers of left ventricular fibrosis and heart failure in aortic stenosis; and (ii) myocardial fibrosis as a predictor of postoperative outcome.
  
  
  METHODS
  Among a total of 132 patients (mean age 68 +/- 10 years) with severe aortic stenosis, measurements were made of circulating N-terminal propeptide of procollagen I (PINP), C-terminal telopeptide of collagen I (CITP) and N-terminal propeptide of procollagen III (PIIINP). Cardiac catheterization, echocardiography and a 6-min walk test were also performed. The aorta-to-coronary sinus concentration gradients of collagen metabolites were determined in 45 patients. Patients free from coronary artery disease (n = 85) underwent left ventricular biopsies for the assessment of myocardial fibrosis, one-year postoperative echocardiography and a 6-min walk test, and a long-term follow up for mortality.
  
  
  RESULTS
  Neither peripheral collagen metabolites nor their transcardiac concentration gradients correlated with the extent of myocardial fibrosis. PIIINP demonstrated a net release from the heart, while PINP and CITP showed consistent falls in transcardiac concentrations that suggested extraction rather than release by the heart. Peripheral PIIINP correlated directly with the pulmonary wedge pressure (r = 0.50, p < 0.001) and inversely with the left ventricular ejection fraction (r = -0.40, p = 0.00001) and 6-min walk (r = -0.29, p = 0.001). Similar associations with heart failure were found for CITP, but not for PINP. One-year postoperative changes in exercise capacity and left ventricular mass and function were independent of myocardial fibrosis, as was mortality over a median of 8.8 years.
  
  
  CONCLUSIONS
  Circulating collagen metabolites are not reliable surrogate measures of myocardial fibrosis in aortic stenosis, despite CITP and PIIINP being associated strongly with heart failure and left ventricular dysfunction. The results of surgery, including long-term survival, appear independent of the extent of myocardial fibrosis.
authors.affiliation: Division of Cardiology, Helsinki University Central Hospital, Helsinki, Helsinki, Finland. markku.kupari@hus.fi
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
authors.forename: Mika
authors.initials: M
authors.lastname: Laine
authors.forename: Heikki
authors.initials: H
authors.lastname: Turto
authors.forename: Jyri
authors.initials: J
authors.lastname: Lommi
authors.forename: Kalervo
authors.initials: K
authors.lastname: Werkkala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000150:complications / Q000601:surgery; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000097:blood* / Q000209:etiology; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide